This application is submitted as a competitive renewal of a midcareer investigator award in patient-oriented research (K24CA82450). The PI is Randall F. Holcombe, MD. This application details the experience, qualifications and short- and long-term patient-oriented research plans of Dr. Holcombe, as well as reviews progress during the period of support under the current award. Details about current and planned patient- oriented research is provided. These studies are focused on patient-oriented research in colon cancer and include studies related to the Wnt signaling pathway, elucidation of immunologic events in conjunction with administration of chemotherapy for colon cancer and definition of the mechanisms and potential therapeutic and cancer preventive effects of resveratrol, a naturally occuring compound found in the skin of grapes. Patients with inflammatory bowel disease, having or at high risk for colon cancer, are also studied. An additional clinical trial with laboratory correlative studies, originally designed and written by a mentee hematology-oncology fellow of Dr. Holcombe's involves the treatment of patients with gastric cancer. Mentoring activity over the past 5 years and mentoring plans for the next 5 years are described. The accomplishments of mentees are outlined as are their current activities, espeicially as related to ongoing participation in patient-oriented research. Ongoing mentoring plans include formal coursework, basic/translational research experiences, instruction in the development and implementation of clinical research trials, and hands-on experiences in clinical research. The original goals and objectives of the current award are reviewed and the extent to which these have been achieved is delineated. Documentation of institutional support and justification of the need for continued support through the K24 mechanism is provided.